Distinct roles for canonical and variant histone H3 lysine-36 in Polycomb silencing.
Distinct roles for canonical and variant histone H3 lysine-36 in Polycomb silencing.
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DOI：
10.1126/sciadv.adf2451
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发表时间：
2023-03
期刊：
影响因子：
13.6
通讯作者：
Matera, A. Gregory
中科院分区：
文献类型：
--
作者：
Salzler, Harmony R.;Vandadi, Vasudha;McMichael, Benjamin D.;Brown, John C.;Boerma, Sally A.;Leatham-Jensen, Mary P.;Adams, Kirsten M.;Meers, Michael P.;Simon, Jeremy M.;Duronio, Robert J.;McKay, Daniel J.;Matera, A. Gregory
多梳复合物通过靶基因的可遗传沉默来调节细胞类型特异性基因表达程序。组蛋白H3赖氨酸27（H3K27me3）的三甲基化对于这一过程至关重要。H3K36的扰动被认为会干扰H3K27me3。我们发现，果蝇复制依赖型（H3.2K36R）或复制非依赖型（H3.3K36R）组蛋白H3基因的突变体通常保持Polycomb沉默，并达到发育的后期阶段。相比之下，组合（H3.3K36RH3.2K36R）突变体显示广泛的Hox基因的错误表达，并未能发展过去的第一个幼虫阶段。染色质分析显示，H3.2K36R突变在整个沉默结构域中广泛破坏H3K27me3水平，而这些区域在H3.3K36R动物中大多不受影响。H3.3分布的分析表明，这种组蛋白是丰富的假定Polycomb响应元件位于沉默域的外部，但相对耗尽的内部。我们的结论是，H3.2和H3.3 K36残基合作，抑制Hox基因使用不同的机制。组蛋白H3.2和H3.3 K36残基确保Hox基因沉默，并通过不同但协同的机制实现发育。
Polycomb complexes regulate cell type–specific gene expression programs through heritable silencing of target genes. Trimethylation of histone H3 lysine 27 (H3K27me3) is essential for this process. Perturbation of H3K36 is thought to interfere with H3K27me3. We show that mutants of Drosophila replication-dependent (H3.2K36R) or replication-independent (H3.3K36R) histone H3 genes generally maintain Polycomb silencing and reach later stages of development. In contrast, combined (H3.3K36RH3.2K36R) mutants display widespread Hox gene misexpression and fail to develop past the first larval stage. Chromatin profiling revealed that the H3.2K36R mutation disrupts H3K27me3 levels broadly throughout silenced domains, whereas these regions are mostly unaffected in H3.3K36R animals. Analysis of H3.3 distributions showed that this histone is enriched at presumptive Polycomb response elements located outside of silenced domains but relatively depleted from those inside. We conclude that H3.2 and H3.3 K36 residues collaborate to repress Hox genes using different mechanisms. Histone H3.2 and H3.3 K36 residues ensure Hox gene silencing and enable development by different, but synergistic mechanisms.
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影响因子：
14.9
作者：
Bredesen, Bjorn Andre;Rehmsmeier, Marc
通讯作者：
Rehmsmeier, Marc
影响因子：
64.5
作者：
Banaszynski LA;Wen D;Dewell S;Whitcomb SJ;Lin M;Diaz N;Elsässer SJ;Chapgier A;Goldberg AD;Canaani E;Rafii S;Zheng D;Allis CD
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作者：
Buchenau, P;Hodgson, J;Strutt, H;Arndt-Jovin, DJ
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Arndt-Jovin, DJ
影响因子：
16
作者：
Chaouch, Amel;Berlandi, Johannes;Chen, Carol C. L.;Frey, Felice;Badini, Shireen;Harutyunyan, Ashot S.;Chen, Xiao;Krug, Brian;Hebert, Steven;Jeibmann, Astrid;Lu, Chao;Kleinman, Claudia L.;Hasselblatt, Martin;Lasko, Paul;Shirinian, Margret;Jabado, Nada
通讯作者：
Jabado, Nada
DOI：
10.1073/pnas.172403699
发表时间：
2002-12-10
影响因子：
11.1
作者：
Ahmad, K;Henikoff, S
通讯作者：
Henikoff, S